Embelin potentiates venetoclax-induced apoptosis in acute myeloid leukemia cells
Copyright © 2021 Elsevier Ltd. All rights reserved..
Acute myeloid leukemia (AML) belongs to a group of hematological cancer whose relapse cases are often associated with chemoresistance that impairs treatment success and contributes to a poor outcome. For this reason, there is an urgent need for the development of new therapeutic strategies. Herein, we explore the combination of venetoclax, a BCL2 inhibitor, and embelin, an XIAP inhibitor, in the AML cell lines. Combinatory treatment of venetoclax and embelin potentiated cytotoxic effects of these drugs, demonstrating that both in combination present lower IC50 values than single treatment of either venetoclax or embelin alone in both cell lines analyzed. The combinatory treatment further increased the apoptosis-inducing properties of both compounds. Computer simulations suggest that embelin binds to both BIR2 and BIR3 domains of XIAP, reinforcing this inhibitory apoptosis protein as an embelin target. Although all AML cell lines presented similar basal levels of XIAP, the combinatory treatment effectively inhibited XIAP expression in OCI-AML3 cells. In conclusion, the inhibition of both apoptosis inhibitory players, BCL2 and XIAP, by venetoclax and embelin, respectively, potentiated their cytotoxic effects in AML cell lines.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:76 |
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| Enthalten in: |
Toxicology in vitro : an international journal published in association with BIBRA - 76(2021) vom: 24. Okt., Seite 105207 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Reis-Silva, Catarina Sofia Mateus [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 20.01.2022 Date Revised 20.01.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.tiv.2021.105207 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Copyright © 2021 Elsevier Ltd. All rights reserved. | ||
| 520 | |a Acute myeloid leukemia (AML) belongs to a group of hematological cancer whose relapse cases are often associated with chemoresistance that impairs treatment success and contributes to a poor outcome. For this reason, there is an urgent need for the development of new therapeutic strategies. Herein, we explore the combination of venetoclax, a BCL2 inhibitor, and embelin, an XIAP inhibitor, in the AML cell lines. Combinatory treatment of venetoclax and embelin potentiated cytotoxic effects of these drugs, demonstrating that both in combination present lower IC50 values than single treatment of either venetoclax or embelin alone in both cell lines analyzed. The combinatory treatment further increased the apoptosis-inducing properties of both compounds. Computer simulations suggest that embelin binds to both BIR2 and BIR3 domains of XIAP, reinforcing this inhibitory apoptosis protein as an embelin target. Although all AML cell lines presented similar basal levels of XIAP, the combinatory treatment effectively inhibited XIAP expression in OCI-AML3 cells. In conclusion, the inhibition of both apoptosis inhibitory players, BCL2 and XIAP, by venetoclax and embelin, respectively, potentiated their cytotoxic effects in AML cell lines | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Acute myeloid leukemia | |
| 650 | 4 | |a Apoptosis | |
| 650 | 4 | |a Embelin | |
| 650 | 4 | |a Venetoclax | |
| 650 | 7 | |a Antineoplastic Agents |2 NLM | |
| 650 | 7 | |a Benzoquinones |2 NLM | |
| 650 | 7 | |a Bridged Bicyclo Compounds, Heterocyclic |2 NLM | |
| 650 | 7 | |a Proto-Oncogene Proteins c-bcl-2 |2 NLM | |
| 650 | 7 | |a Sulfonamides |2 NLM | |
| 650 | 7 | |a X-Linked Inhibitor of Apoptosis Protein |2 NLM | |
| 650 | 7 | |a venetoclax |2 NLM | |
| 650 | 7 | |a N54AIC43PW |2 NLM | |
| 650 | 7 | |a embelin |2 NLM | |
| 650 | 7 | |a SHC6U8F5ER |2 NLM | |
| 700 | 1 | |a Branco, Paola Cristina |e verfasserin |4 aut | |
| 700 | 1 | |a Lima, Keli |e verfasserin |4 aut | |
| 700 | 1 | |a Silva, Fabiana Lima |e verfasserin |4 aut | |
| 700 | 1 | |a Moreno, Paulo Roberto Hrihorowitsch |e verfasserin |4 aut | |
| 700 | 1 | |a Guallar, Victor |e verfasserin |4 aut | |
| 700 | 1 | |a Costa-Lotufo, Leticia Veras |e verfasserin |4 aut | |
| 700 | 1 | |a Machado-Neto, João Agostinho |e verfasserin |4 aut | |
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